The Structure of the Aflatoxin B₁-DNA Adduct at N7 of Guanine. Theoretical Intercalation and Covalent Adduct Models

Aflatoxin B1 and DNA Adducts. Proposed Model for Surface Noncovalent and Covalent Complexes with N(7) of Guanine. II.

“…For AFB 1 , the surface association confines it to the rna jor groove as distinguished from internal or intercalative associations arising from its interactions with and between base pairs. These surface AFB 1 interactions are comparable to the previously reported intercalative and intercalative covalent AFB 1 -DNA associations (7). The exact conformational properties of the AFB 1 -DNA adducts are presently unknown from any experimental data.…”

“…Two previous studies (7,14) reveal the possibility of surface active ( noncovalent and covalent) AFB 1 with N(7) of guanine in the 5'-GGGG-3' model tetramer duplex. Surface association is defined as an association, noncovalent or covalent, in which the interacting specie interacts with the DNA along the surface of the helix.…”

“…These intercalative covalent adduct sites adse from the proposed intercalative interaction of AFB 1 preceding the covalent event (7). The theoretically proposed intercalative association model also follows the BP2,5' and BP3,3' conformational site interactions.…”

“…However, one study questions intercalative interactions between AFB 1 and DNA (11). Two other experimental studies provide evidence of precovalent intercalation of AFB 1 in DNA (12) and an intercalative covalent adduct in which the AFB 1 moiety intercalates to the 5' side of the targeted guanine (13) as proposed in independent theoretical study (7). …”

“…Previous studies (7)(8)(9)(10) show that AFB 1 preferentially covalently bonds to the second and third guanine bases of a 5' -GGGG-3' sequence of DNA Additionally, AFB 1 's attack at the second G base (from the 3' end) leads to conformational site adducts designated as base pair two, 5' (BP2,5') or from the 5' -end, base pair three, 3' (BP3,3'). These intercalative covalent adduct sites adse from the proposed intercalative interaction of AFB 1 preceding the covalent event (7).…”